The purpose of this study is to evaluate the differences in pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite depending on the strategy of the drug administration in patients with unstable angina pectoris.

On the basis of the current guidelines ticagrelor is a recommended antiplatelet agent in acute coronary syndromes, including unstable angina pectoris.

According to the results of the MOJITO study, performed in patients with ST-elevation myocardial infarction, the effect of ticagrelor, measured as platelet inhibition, may be achieved sooner when crushed tablets are administered. Thus, there may be significant differences in pharmacokinetics and pharmacodynamics of ticagrelor if pulverized drug is given orally or sublingually when compared with currently used oral administration of integral tablets.

The study is designed as an open-label, single-center, randomized trial of different strategies of administration of ticagrelor in patients with unstable angina pectoris. After enrollment, the participants will be randomized into three arms, each receiving ticagrelor. The drug will be given in: (1) pulverized tablets administered sublingually, (2) pulverized tablets administered orally or in (3) integral tablets orally. The time required for ticagrelor and its active metabolite AR-C124900XX to reach their maximum serum concentration will be measured as the primary outcome of the study. Moreover, further evaluation of other parameters including maximum plasma concentration and area under the plasma concentration of ticagrelor and its active metabolite will be assessed as secondary outcomes. The platelet reactivity will be measured with the Multiplate Analyzer.

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures
• Diagnosis of unstable angina
• Male or non-pregnant female, aged 18-80 years old
• Provision of informed consent for angiography and percutaneous coronary intervention (PCI)
• GRACE score <140 pts

Exclusion Criteria:

• treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment
• hypersensitivity to ticagrelor
• current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin
• active bleeding
• history of intracranial hemorrhage
• recent gastrointestinal bleeding (within 30 days)
• history of coagulation disorders
• platelet count less than <100 x10^3/mcl
• hemoglobin concentration less than 10.0 g/dl
• history of moderate or severe hepatic impairment
• history of major surgery or severe trauma (within 3 months)
• patients considered by the investigator to be at risk of bradycardic events
• second or third degree atrioventricular block during screening for eligibility
• history of asthma or severe chronic obstructive pulmonary disease
• patient requiring dialysis
• manifest infection or inflammatory state
• Killip class III or IV during screening for eligibility
• respiratory failure
• history of severe chronic heart failure (NYHA class III or IV)
• concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment
• body weight below 50 kg